This is an application for continuation of funding for the Cleveland Pediatric Pharmacology Research Unit (PPRU). The unit was first funded in September 1994, one year after the establishment of the PPRU Network by NIH and has been funded since that time at only one half the level of the other units in the Network. Despite this funding bias, the Cleveland PPRU has been an active member of the Network for the past 3 1/2 years, participating in 13 network protocols by enrolling 298 patients. In fact, the Cleveland PPRU has been the innovating site for 5 of the completed or ongoing network protocols; 3 with industry funding and sponsorship. Our unit also planned, obtained sponsorship and held the joint PPRU/European Society of Developmental Biology Symposium entitled "The Therapeutic Orphan - 30 Years Later." The proceedings are due to be submitted for publication in the near future. In seeking continued funding for our PPRU, we intend that the unit continue its intimate relationship with the Center for Drug Research of the Department of Pediatrics at Case Western Reserve University. This Center has been involved in the pre NDA evaluation of virtually every drug and vaccine labeled for infants and children in the past 15 years. The Cleveland PPRU is not only prepared because of its personnel and patient resources to participate in the current and future network protocols, but, with this request for renewed funding will bring additional assets to the Network. First, this application brings a new level of institutional commitment to the PPRU and pediatric clinical trials with the establishment of the Center for Drug Research Advisory Board under the leadership of the Department of Pediatrics Vice-Chair for Research. This Board will ensure participation of all of the child health specialties in this clinical research program. Our unit has also greatly expanded both is pharmacokinetic and modeling capabilities through collaboration with Dr. Drusano and his group, and our data management and analysis capabilities through amalgamation of our PPRU Biostatistics/Pharmacokinetics Core into a new Division of Clinical Epidemiology within the Department of Pediatrics. Lastly, through the research proposals included, we intend to develop a foundation that will further extend the Network capabilities into the areas of molecular pharmcoepidemiology, pharmacokinetic/pharmacodynamic modeling, translational research involving new molecular entity discovery and its clinical application to infants and children as well as the interface of pharmacogenetics with functional genomics. All these technologies will be crucial to the future of pediatric therapeutics and drug labeling for infants and children.